To investigate the safety and the efficacy of perampanel in patients with sporadic amyotrophic lateral sclerosis.

There are limited treatments for amyotrophic lateral sclerosis (ALS). Perampanel, selective non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist, has been reported to rescue motor dysfunction and neuropathology in sporadic ALS model mice, in which is an RNA editing enzyme adenosine deaminase acting on RNA 2 is conditionally knocked out in motor neurons, suggesting therapeutic potency of perampanel for sporadic ALS.

We conducted a multicenter randomized, double-blinded, placebo-controlled, parallel-group phase 2 clinical trial to evaluate the efficacy and safely of perampanel at doses of 4mg and 8mg per day, as compared with placebo, in patients with sporadic ALS. Sporadic ALS patients, aged 40 years to 78 years who have clinically definite ALS, clinically probable ALS, or clinically probable-laboratory supported ALS as a specified in the revised El Escorial Airline House diagnostic criteria, were registered. The primary outcome measure is the change in ALS functional rating scale-revised (ALSFRS-R) scores after 48 weeks of the treatment. Secondary outcomes include change in ALSFRS-R slope, manual muscle test, and percent-predicted forced vital capacity. Mixed effect model repeated measures analysis was used for statistics.

Of 79 patients eligible for interim registration, 66 patients underwent randomization to assign to 3 groups: 8mg of perampanel, 4mg of perampanel, and placebo. This study will be completed in January 2020. The results this study will be available in February 2010. (Funded by Japan Agency for Medical Research and Development, AMED; CrinicalTrials.gov number, NCT03019419.)

The conclusions will be updated at the 72^nd annual meeting of Â鶹´«Ã½Ó³»­.